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Introduction

A cancer diagnosis and its treatment can affect the lives of people who have or have had cancer (that is, cancer survivors) in many ways, often over long periods of time. Fortunately, recent progress in cancer research has yielded new knowledge about cancer biology and resulted in a number of innovative treatments for people who have cancer. This report is an overview of the current status of the diagnosis, treatment, and prognosis of select common adult cancers, particularly breast cancer and lung cancer, and their effects on the health and functioning of people with cancer.

Cancer is a group of diseases characterized by uncontrolled growth in which the body’s cells divide without stopping and spread into surrounding tissues, often forming solid masses known as tumors (NCI, 2016). It is the second leading cause of death in the United States after heart disease (CDC, 2020a), and it was estimated that in 2020 more than 1.8 million new cases of cancer were diagnosed and more than 600,000 deaths occurred from it (Siegel et al., 2020).¹ Cancer is a major public health problem: the lifetime probability for developing cancer in the United States is about 40% in males and about 39% for females (Siegel et al., 2020).

The cancer diagnosis and treatment landscape has changed dramatically in the past two decades, reflecting basic science discoveries in genetics

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¹ The committee notes that this estimate was made before the coronavirus disease 2019 (COVID-19) pandemic began in early 2020 in the United States. In the United Kingdom it has been estimated that there may be approximately 5–17% additional deaths from breast, lung, esophageal, and colorectal cancers over the next 5 years as a result of delayed diagnosis due to COVID-19 (Maringe et al., 2020).

and immunology that occurred at the beginning of this century (e.g., the Human Genome Project). These discoveries have transformed scientific understanding of cancer biology and resulted in new diagnostic and treatment strategies that are now in regular clinical use. During the past century, cancer treatment planning focused almost solely on the anatomic extent of cancer, best characterized by a staging system that quantifies tumor size, as well as the extent of regional and distant spread. Now pathologists identify the unique expression of a tumor’s genetic and immune features on an initial biopsy so that this information can be incorporated with traditional diagnostic approaches to chart a personalized treatment plan for the patient. These changes are exemplified by the contemporary management of breast cancer and lung cancer but are also seen across a broad range of other cancers, several of which are also discussed briefly in this report. There is considerable excitement about these new and emerging treatments (e.g., targeted therapies, immunotherapy).

However, much less is known about the long-term and late-onset effects of these treatments compared with the conventional approaches to surgery, chemotherapy, and radiation that have been used for more than 50 years.

While cancer remains a major cause of mortality in the United States, improvements in cancer treatment and survival are leading to increasing numbers of cancer survivors. While the definition of “cancer survivor” has sometimes varied, this term generally includes anyone with a history of cancer and is used from the time of diagnosis until death (see Box 1-1).

Although all individuals diagnosed with cancer can be considered cancer survivors, in this report the committee also uses the term “cancer patients” to describe cancer survivors who are engaged in active cancer treatment.

Cancer death rates have decreased every year during the past 20 years, for an overall drop of 26% between 1999 and 2018 (CDC, 2020b). There are currently 17 million cancer survivors (Miller et al., 2019), and this number is expected to grow to 26 million by 2040 (Bluethmann et al., 2016). More than one-third of cancer survivors are between 20 and 64 years of age (Miller et al., 2019). Survival rates have improved significantly, with the 5-year survival rate for all cancers increasing from 50% in 1981–1983 to 69% in 2005–2008 (NCI, 2019a). During this period, there was an even larger increase in the 5-year survival rate for some specific cancers, such as leukemia, which improved from 37% to 62% (NCI, 2019a). In 2019, 67% of survivors (10.3 million) had survived 5 years or more after diagnosis; 45% had survived 10 years or more; and 18% had survived 20 years or more (ACS, 2019) (see Table 1-1).

To help address the needs of the growing population of child and adult cancer survivors, in 1996 the National Cancer Institute (NCI) established the Office of Cancer Survivorship (NCI, 2020). The mission of the office is to support further study and to fund research focused on the physical and emotional challenges faced by cancer survivors in the years after their initial diagnosis and treatment. Research funded by NCI and other organizations has highlighted the ongoing morbidities experienced by many cancer survivors, with concomitant declines in both physical and mental health, as well as the challenges they face in taking part in normal activities, including

TABLE 1-1 Estimated Number of U.S. Cancer Survivors by Sex and Years Since Diagnosis

SOURCE: Adapted from ACS (2019) with permission. Based on data from Surveillance Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, as of January 1, 2019.

work. Regardless of the time since diagnosis, cancer survivors report poorer health and more comorbidities than people who have never had cancer (Yabroff et al., 2004).

Cancer-related impairments and functional limitations can be caused by the cancer itself (e.g., compromised breathing from a tumor’s direct invasion of the lungs or difficulty walking because of a brain tumor), or they may be caused by cancer treatments such as surgery, radiation therapy, and systemic therapy, or they may be due to a combination of both the cancer and its treatment. Cancer treatment–related impairments include those that may develop during treatment but resolve when the treatment or healing is complete (acute effects), such as postoperative pain, as well as those that develop during treatment and become chronic (long-term effects), such as chronic neuropathy following chemotherapy, persistent fatigue, or lymphedema. Some impairments, such as radiation fibrosis syndrome, may not be evident during treatment but may develop weeks, months, or even years after the cancer treatment is complete (late-onset effects). In turn, these late-onset impairments may result in secondary impairments such as fatigue which may also limit a person’s functioning (NASEM, 2020a).

As the number of cancer survivors grows, there is increased interest in how cancer and its treatments may affect a person’s ability to work, whether the person has maintained employment throughout the treatment or is returning to work at a previous, current, or new place of employment. Return to work is a particularly important and salient issue since the median age for a cancer diagnosis in the United States is 66 years (SEER, n.d.) and thus approximately half of all newly diagnosed cancer patients are of working age (de Boer et al., 2009; Short et al., 2005). In a meta-analysis de Boer et al. (2009) found that the relative risk of receiving a disability benefit or otherwise being disabled for work was almost three times higher for cancer survivors than for individuals without a history of cancer. The improved survival rates that have resulted from new and emerging treatments mean that cancer survivors are living longer but may also experience long-term and late-onset impairments from those treatments for a longer period of time. In turn, longer periods of impairment may have consequences for cancer survivors’ ability to work because of such factors as their increased need for workplace accommodations, occupational supportive care throughout treatment, and disability benefits for a longer time than previously expected (Kiasuwa Mbengi et al., 2016).

The most common cancers in terms of the numbers of estimated new cases diagnosed in 2020 are listed in Box 1-2 (see Chapter 3 for more information on number of cases by cancer and sex). While all of these cancers and their treatments have the potential to cause disability, some cancers and treatments are more likely to cause disability than others, depending on the cancer site, cancer stage, and severity and duration of treatment as well as

other clinical factors, including comorbidities. For example, Horsboel et al. (2014) found that patients with hematological cancers have an increased risk of requiring disability than patients who have other cancers, possibly as a result of treatment with intensive chemotherapy and bone marrow transplants.

A cancer survivor’s ability to remain employed may also be influenced by sociodemographic factors including personal factors (age, education, sex, or race) and work-related/social factors (employment type and physical demands, company size, or amount of social support) (Endo et al., 2020). de Boer et al. (2009) found that cancer survivors were more likely to be unemployed than individuals without cancer (33.8% compared with 15.2%), particularly survivors of breast cancer, gastrointestinal cancers, and cancers of the female reproductive organs. The negative effects of long-term unemployment include a decreased quality of life and lower self-esteem as well as a level of financial distress that can cause other detrimental effects (Beesley et al., 2018; van der Noordt et al., 2014; Verbeek et al., 2003; Zagozdzon et al., 2014). To help alleviate financial concerns, cancer patients and survivors who are unable to work because of cancer-related impairments have the option to apply for disability benefits from the U.S. Social Security Administration (SSA).

When cancer patients and survivors apply for disability benefits, SSA is required by the Social Security Act to determine their eligibility and, if they are approved, provide them monetary benefits (see Chapter 2). The 1990 Americans with Disabilities Act² (ADA) prohibits discrimination based on certain disabilities in the workplace and requires employers

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² Americans with Disabilities Act of 1990, 42 U.S.C. Chapter 126 § 12101 (1990).

to provide reasonable accommodations for individuals with disabilities in order for them to perform their job duties. While both of these laws were enacted to help disabled individuals, they have differing purposes and eligibility requirements. For example, receiving disability benefits from SSA is based on one’s inability to work, perform basic job duties, or engage in any other kind of substantial gainful activity; thus, SSA disability benefits provide the necessary support to people who can no longer work as a result of their health. Conversely, the ADA protections benefit individuals who can still perform essential parts of their jobs but may need reasonable accommodations from their employers—such as providing a reasonable amount of additional unpaid leave for medical treatment, making existing facilities usable by disabled employees, or allowing a flexible work schedule—to do so³ (Greidanus et al., 2018; Williams-Whitt et al., 2016). Research has shown that employers can play an essential role in promoting the work participation of cancer survivors, with supervisor support being an important return-to-work facilitator. In order to make the correct disability decisions, SSA disability programs need to reflect current medicine as well as the evolution of work. A more detailed discussion of the SSA disability determination process can be found in Chapter 2.

COMMITTEE’S CHARGE

In order to keep the information on which it bases its disability listings as current as possible, in 2019 SSA asked the National Academies of Sciences, Engineering, and Medicine (the National Academies) to convene a committee of experts to provide an overview of the diagnosis, treatment, and prognosis of selected adult cancers, particularly breast cancer and lung cancer (see Box 1-3 for the committee’s complete Statement of Task). This report is intended to provide SSA with background information on breast cancer, lung cancer, and selected other cancers to assist in its review of the Listing of Impairments for disability assessments.

SSA asked the National Academies study committee to address several specific topics, including determining the latest standards of care as well as new technologies for understanding disease processes, treatment modalities, and the effect of cancer on a person’s health and functioning, in order to inform SSA’s evaluation of disability claims for adults with cancer. The study committee was asked to not examine access to care for diagnosing and treating cancer, and it was asked to not make recommendations based on its overview of the current status of cancer diagnosis, treatment, or prognosis.

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³ SSR 00-1c (Jan 7, 2000).

COMMITTEE’S APPROACH

To accomplish the Statement of Task, the National Academies empaneled a committee of 15 members with expertise in the areas of the diagnosis and treatment of breast cancer, lung cancer, hematologic cancers, and colorectal cancer; radiation oncology; cancer survivorship and rehabilitation; long-term and late-onset effects of cancer and its treatment; cognitive impairment; primary care; mental health; and epidemiology (see Appendix A for the biographical sketches of the committee members).

The committee held five meetings that included two public sessions. At the first public session SSA provided more specifics on its objectives for the study, and the committee heard from a researcher studying the impact of cancer on employment and productivity. At the second public session the committee heard from four cancer survivorship advocates and held a panel discussion to explore more fully the impact of cancer and its treatment on long-term impairments, functional limitations, and quality of life during and after cancer treatment (see Appendix B for the public session agendas).

In addition, the committee conducted an extensive review of the literature pertaining to the selected cancers in adults, including literature specific to cancer diagnosis, treatment, and functional outcomes. Committee members and project staff identified additional literature and information using traditional academic research methods and online searches throughout the course of the study.

The committee’s work was further informed by previous National Academies reports related to disability and to cancer, which are referenced throughout the report. In addition, the National Academies recently completed a study for SSA on childhood cancers and disability that reviewed the status of the diagnosis, treatment, and prognosis of common select childhood cancers, in the U.S. population under 18 years of age and identified the relative levels of functional limitation typically associated with the cancers, their common treatments, and other considerations (NASEM, 2020b).

POPULATION OF INTEREST AND SELECTION OF CANCERS

Cancer survivors between the ages of 18 and 65 years are an important population for SSA because these working-age adults have complex responsibilities, including family caregiving, as well as educational activities, employment pressures, and financial needs. These individuals may also experience certain challenges related to cancer and its treatment more frequently than those younger than 18 years or older than 65 years. For example, adults who have cancer at a younger age are likely to have higher rates of cancer-related pain (Lundstedt et al., 2012; Macdonald et al., 2005; Schou Bredal et al., 2014), lower quality of life (Champion et al., 2014;

Green et al., 2011; Kroenke et al., 2010), and higher levels of financial hardship (Banegas et al., 2016; Guy et al., 2014; Yabroff et al., 2016) than those who have cancer at older ages.

The highest incidence rates of cancer in working-age adults are for breast, colorectal, lung, melanoma of the skin, lymphoma, and leukemia (based on age-adjusted incidence SEER data, 2012–2016; see Chapter 3). Innovations in new cancer treatments and standards of care, most notably in breast and lung cancer, may substantially affect the long-term outcomes in these adult survivors.

SSA asked the National Academies committee to focus on breast cancer and lung cancer, but it also asked that the committee consider other cancers for which changes in incidence, diagnosis, treatment, or prognosis are occurring. Thus, the committee addressed those cancers most prevalent in SSA’s disability claims (for more information on SSA disability claims, see Chapter 2). For example, although prostate cancer is the third most common cancer diagnosed in the United States in 2020 (an estimated 191,930 new cases), it is not among the most common cancers listed in SSA disability claims, nor is it frequently diagnosed in men under the age of 65 (NCI, 2019b; Siegel et al., 2020); therefore, it is not discussed in this report.

Although SSA provides benefits for children with cancer who are disabled, these children are not considered in this report as SSA assesses their disabilities differently than it does for adults who have cancer. The committee recognizes that adult survivors of pediatric cancers may experience long-term impairments and subsequent functional limitations, including the development of new cancers. The committee considers these new cancers in the same manner as cancers that develop in adults. Pediatric cancers and their associated impairments are examined in the 2020 National Academies report Childhood Cancer and Functional Impacts Across the Care Continuum (NASEM, 2020b).

ORGANIZATION OF THE REPORT

Providing an overview of the current status of the diagnosis, treatment, and prognosis of breast, lung, and other selected adult cancers was a complex task. New technologies and an improving understanding of the biology of cancer are resulting in rapid advances in both the diagnosis and the treatment of these cancers, which in turn are affecting the long-term outcomes for cancer survivors. To address these issues, the committee began by requesting information from SSA on what cancers are most frequently encountered in the disability claims it receives. SSA’s process for determining disability and the detailed information it provided on the cancers it most frequently reviews are presented in Chapter 2. However, SSA’s most common cancers do not necessarily parallel those seen in the general U.S.

population. Chapter 3 compares the epidemiology of SSA’s most common cancers with the U.S. population’s most common cancers. The chapter provides information on the incidence of new cases, mortality rates, and survival from the cancers most common in SSA disability claims. An overview of the diagnosis and treatment of adult cancers, with an emphasis on current standards of care as recommended in clinical practice guidelines, is given in Chapter 4. This chapter also discusses the screening for and staging of cancer as well as cancer prognosis. Chapters 5 and 6 build on the standards of care in Chapter 4 and apply them to breast cancer and lung cancer, respectively. There are four major subtypes of breast cancer and two major subtypes of lung cancer. Differences in the staging, diagnosis, treatment, and prognosis of the several subtypes are described, and the implications for the long-term outcomes for survivors of these cancers are assessed. Treatments for these cancers include surgery, radiation, and systemic treatments, and their use for each cancer and subtype is explained. To address SSA’s request that the committee also consider other cancers as appropriate, Chapter 7 highlights new information on the incidence and treatment of several cancers frequently seen in SSA disability claims, including gastrointestinal cancers (colorectal, pancreatic, and liver and bile duct cancers), hematologic cancers (leukemias, lymphomas [Hodgkin and non-Hodgkin], and myelomas), ovarian cancer, head and neck squamous cell cancers, and melanoma of the skin. The committee included the last cancer because it is a commonly diagnosed cancer in the U.S. population (see Box 1-2) and new advances in treatment have greatly improved its prognosis, which may affect future SSA disability claims. Chapter 8 provides an overview of the many new and emerging therapies that are being tested in clinical trials. The committee distinguishes between new treatments—those already approved by the U.S. Food and Drug Administration for some cancers, and now being explored as potential treatments for other cancers—and emerging treatments, or those that are not yet approved but are in clinical trials to determine their effectiveness and safety. Although the committee focuses on pharmaceutical agents in this chapter, it also considers new approaches for surgery and radiation therapies. The various treatments discussed in Chapters 4 through 8 all have some level of deleterious effects on cancer survivors as does cancer itself. The long-term and late-onset adverse effects of cancer and its treatments (impairments) are assessed in Chapter 9. While some treatments may have few lasting effects, others such as radiation, chemotherapy, and targeted therapy agents can have prolonged impacts on a survivor’s functioning which may not resolve for months or years or which may last a lifetime. Cancer-related impairments may affect both physical and mental health, and their prevalence, diagnosis, treatment, and prognosis are considered in this chapter. Chapter 10 looks at the future of cancer

survivorship and what can be done by cancer survivors, caretakers, health care professionals, and organizations to ensure that the survivors receive the care necessary for their optimal functioning after their diagnosis. The concept of cancer survivorship is becoming more widely acknowledged, and more people are recognizing that a diagnosis of cancer is no longer a death sentence, even though the effects of cancer and its treatment may be evident for years. Finally, Appendix A presents short biographical sketches of the committee members and consultant, and Appendix B contains the agendas for the committee’s public sessions.

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